What is the pharmacology of Rocuronium (a non-depolarizing neuromuscular blocking agent) in patients with impaired renal or hepatic function?

Rocuronium Pharmacology in Renal and Hepatic Impairment

Rocuronium can be used at standard initial doses in both renal and hepatic impairment without dose adjustment, though duration of action will be prolonged in hepatic disease. 1

Renal Impairment

No dose adjustment is required for rocuronium in patients with renal dysfunction. 1

• The kidney plays a limited role in rocuronium excretion, allowing usual dosing guidelines to be followed in renal failure 1
• Duration of neuromuscular blockade is not prolonged in renal dysfunction, though substantial individual variability exists (range: 22 to 90 minutes) 1
• Up to 35% of vecuronium (a related aminosteroid) is renally excreted, requiring dose reduction in renal failure, but rocuronium does not share this limitation 2, 3
• For maintenance dosing in severe renal impairment, consider switching to atracurium or cisatracurium due to their organ-independent elimination 4

Hepatic Impairment

Use rocuronium with caution in clinically significant hepatic impairment, as duration of action is moderately to substantially prolonged. 1

Pharmacokinetic Changes in Cirrhosis

• Rocuronium is primarily eliminated by the liver, making hepatic function critical to its clearance 1, 5
• In patients with clinically significant hepatic impairment (n=9), median clinical duration after 0.6 mg/kg was 60 minutes (range: 35-166 minutes) compared to 42 minutes in normal hepatic function 1
• Recovery time was markedly prolonged: median 53 minutes in cirrhosis versus 20 minutes in normal function 1
• The volume of distribution at steady state increases in hepatic impairment, which explains these prolonged effects 1

Dosing Considerations in Hepatic Disease

• Do not modify the initial intubating dose (0.6-1.2 mg/kg) in hepatic impairment, as time to onset remains unchanged 4, 1
• Four of eight cirrhotic patients receiving 0.6 mg/kg under opioid/nitrous oxide/oxygen anesthesia failed to achieve complete block 1
• For rapid sequence intubation in patients with ascites, an increased initial dose may be necessary to ensure complete block, though duration will be prolonged 1
• Doses higher than 0.6 mg/kg have not been studied in hepatic impairment 1
• Up to 50% of vecuronium is excreted in bile, requiring dose reduction in hepatic failure; rocuronium shares similar hepatic elimination pathways 2

General Pharmacology

Mechanism and Potency

• Rocuronium is a monoquaternary aminosteroid non-depolarizing neuromuscular blocking agent with low potency (ED95 approximately 0.3 mg/kg) 2, 6
• The low potency contributes to its rapid onset of action 6, 5
• Greater selectivity for laryngeal muscle systems may explain the rapid onset observed 6
• Unlike vecuronium, rocuronium produces no active metabolites 6, 5

Onset and Duration

• Standard intubating dose of 0.6 mg/kg produces blockade within 60-90 seconds 2, 5
• At 0.6-1.0 mg/kg, maximum blockade occurs within 2-3 minutes 2
• Clinical duration after 0.6 mg/kg is approximately 30-45 minutes in patients with normal organ function 2, 7
• For rapid sequence intubation, doses ≥0.9 mg/kg (preferably 1.0-1.2 mg/kg) provide intubation conditions comparable to succinylcholine 2, 4

Cardiovascular Stability

• Rocuronium demonstrates hemodynamic stability with no significant changes in heart rate, blood pressure, or intracranial pressure 6
• Mild vagolytic effects may occur but are clinically insignificant 5
• No histamine release occurs even at doses as high as 4-5 times ED95 6

Maintenance Dosing

• Continuous infusions begin at 10 μg/kg/min, adjusted to desired degree of blockade 2
• Train-of-four monitoring should guide dosing to achieve 1-2 twitches 8

Critical Pitfalls

• Always provide adequate sedation and analgesia with rocuronium, as it provides no sedation, analgesia, or amnesia 3, 8
• Inadequate sedation during neuromuscular blockade can cause severe patient distress 3
• Prolonged paralysis and skeletal muscle weakness may occur with extended use (>12 hours) 8
• Sugammadex should be immediately available for reversal if needed, particularly in difficult airway situations 2
• Drug interactions with glucocorticoids may cause resistance to rocuronium's effects 9